13087 Anon., 2004. African trypanosomiasis or sleeping sickness - fact-sheet. Weekly Epidemiological Record, 79 (32): 297 - 300.
WHO: Avenue Appia 20, 1211 Geneva 27, Switzerland.
A broad introduction to the disease is given, together with estimates of the geographical extent and the size of the population affected; the reader is warned that the true incidence is grossly underestimated by official statistics.
13088 Buguet, A., Bouteille, B., Cespuglio, R., Bisser, S., Chapotot, F., Bourdon, L., Vincendeau, P., Radomski, M.W. & Dumas, M., 2003. Maladie du sommeil: la recherche oubliée? [Sleeping sickness: has research been forgotten?] Médecine Tropicale, 63 (3): 223 - 227.
Buguet: Institut de médecine tropicale du service de santé des armées, Le Pharo, B.P. 46, 13998 Marseille Armées, France.
To investigate whether HAT has been forgotten as a target for research, a bibliographic database was searched for reports concerning studies in this area. It was found that the number of publications on HAT had remained steady, whereas those on malaria had shown a steady increase. Over 14 years, 1 million Euros had been spent to produce 68 publications recorded in this database.
13089 Iyayi, E.A., Okoruwa, V.O., Babayemi, O.J., Busari, A.A. & Peters, O.F., 2003. Livestock production pattern of agropastoralists in peri-urban centres of south-west Nigeria. Nigerian Journal of Animal Production, 30 (1 - 2): 87 - 92.
Peters: Department of Animal Science, University of Ibadan, Ibadan, Nigeria.
The remarkable reduction of trypanosomiasis and its vector, the tsetse fly, in the South West zone of Nigeria has led to the development of agropastoralism in the zone. This present study was carried out by the administration of structured questionnaires to farmers in three towns (Oyo, Ogbomosho and Saki) in order to highlight some of the factors influencing production in the area. It was found that in all the three towns, animals were maintained on free range grazing, browsing and feeding of crop residues. The most favoured breed kept is the Bunaji, with the highest concentration found in Ogbomosho (52 percent). Labour allocation among agropastoralists was based on sex. Diarrhoea was the most prevalent disease among the adult animals in wet and dry seasons while sand eating was common among the calves. In all the centres, cattle constituted the major ruminant in stock (77 percent) while sheep and goats accounted for 15 and 8 percent, respectively. A preponderance of female cattle over the male for all the breeds was recorded in all the towns. Saki had the highest number of cattle in stock and Oyo the lowest. Feed supplements offered all year round were salt lick and grains. Most of the agropastoralists depended on the use of local herbs and other such methods of combating diseases affecting the herd.
13090 Jannin, J. & Cattand, P., 2004. Treatment and control of human African trypanosomiasis. Current Opinion in Infectious Diseases, 17 (6): 565 - 571.
Access to treatment is a multi-step process and little progress has been made to improve treatments for sleeping sickness over the past 50 years. The current strategy is based on diagnostic tools developed in the 1960s while available drugs are still the same as those developed in the middle of the last century. Strategic opportunities can only be based on two achievements: improved diagnosis and safer drugs. This paper reviews the development of new diagnostic tools and drugs and the opportunity offered by new technologies for their further improvement. The prodrug DB289 shows excellent oral activity with low toxicity for the treatment of early-stage sleeping sickness; it has recently entered phase II(b) clinical trials. The recent ability to identify and test specific host and parasite biomarkers has allowed the development of new diagnostic and stage-determination tools that are more specific and sensitive. The accurate diagnosis of an infection by use of proteomic signature analysis has been achieved. Urinary nitrites and nitrates follow closely the increase of brain nitric oxide associated with the penetration of trypanosomes in the brain. Sleep-onset rapid eye movement-like episodes have been shown to occur at onset of late-stage trypanosomiasis. This unique disturbance of the wake/sleep cycle seems to be the first pathognomonic sign in the occurrence of late-stage trypanosomiasis. Following the description of the disease, and diagnostic tools and drugs that have been used, and are still in use today, the authors show how it has influenced over time the evolution of strategies for surveillance and control. Recent developments and prospects for new, more specific and sensitive diagnostic tools and a safer drug will undoubtedly improve the accuracy of patient recruitment and facilitate treatment, and provide opportunities for new strategies.
13091 Abila, P.P., Kiendrebeogo, M., Mutika, G.N., Parker, A.G. & Robinson, A.S., 2003. The effect of age on the mating competitiveness of male Glossina fuscipes fuscipes and G. palpalis palpalis. Journal of Insect Science, 3 (13): 1 - 8.
Abila: Livestock Health Research Institute (LIRI), P.O. Box 96, Tororo, Uganda. [[email protected]]
The effect of age on male Glossina fuscipes fuscipes and Glossina palpalis palpalis competitiveness were investigated with a view to estimate optimal age for sterile male release. Sterile insect technique involves the mass production, sterilization and sequential release of males of the target species to out compete the wild male population. Mating between released sterile males and wild females produce inviable progeny and the population is reduced over several generations to unsustainable levels. It is vital that the released male be of high quality and are sexually competitive. Age is one parameter affecting the sexual competitiveness of the male tsetse fly. The optimal release age was estimated by assessing sexual competitiveness of flies of different age categories, 1, 5, 8 and 13 days after adult eclosion. A walk-in field-cage was used in order to approximate as closely as possible the actual field scenario during sterile insect release programes. It was shown that 8- and 13-day old males mated significantly more frequently, i.e. were more competitive, in the presence of equal numbers of 1- and 5-day old males. The age of male tsetse flies significantly affected competitiveness in both species studied. The ability of G. f. fuscipes to inseminate was not age dependent, and insemination occurred in all females that mated regardless of male age. In G. p. palpalis, however, 1-day old males were least able to inseminate. Mating duration was not significantly affected by age in both species. Eight to thirteen days are here recommended as the optimal age for males for the sterile male release in the test species.
13092 Abubakar, L.U., Zimba, G., Wells, C., Mulaa, F. & Osir, E.O., 2003. Evidence for the involvement of a tsetse midgut lectin-trypsin complex in differentiation of bloodstream-form trypanosomes. Insect Science and its Application, 23 (3): 197 - 205.
Osir: International Centre of Insect Physiology and Ecology, P. O. Box 30772, Nairobi, Kenya.
A bloodmeal-induced molecule (lectin-trypsin complex) from the midgut of the tsetse fly, Glossina longipennis, with both lectin and trypsin activities, has been previously described. In this paper, the isolation of a similar molecule is reported from the midguts of Glossina fuscipes fuscipes and direct evidence for its involvement in the development of African trypanosomes is provided. The molecule (native Mr ~65,700) has two non-covalently linked subunits, Mr ~28,800 and Mr ~35,700. The native molecule was found to be capable of inducing differentiation of bloodstream-form trypanosomes into procyclic (midgut forms) in vitro. In the assays, specific antibodies against procyclin were used to monitor the transformation of the bloodstream-form trypanosomes into procyclic forms. This induction was specifically inhibited by D-glucosamine. Cis-aconitate was also capable of inducing the transformation process with the same efficiency as that of the lectin-trypsin complex. While increasing the concentrations of the lectin-trypsin complex in the incubation assays resulted in higher transformation rates, it also led to high parasite mortality. These results provide evidence for the involvement of the midgut lectin-trypsin complex in the differentiation of bloodstream-form trypanosomes within the tsetse midgut.
13093 Aksoy, S., Berriman, M., Hall, N., Hattori, M., Hide, W. & Lehane, M.J., 2005. A case for a Glossina genome project. Trends in Parasitology, 21 (3): 107 - 111.
Aksoy: Yale University School of Medicine, 60 College Street, 606 LEPH, New Haven, CT 06520, USA.
Given the medical and agricultural significance of Glossina, knowledge of the genomic aspects of the vector and vector-pathogen interactions has a high priority. In preparation for a full genome sequence initiative, an extensive set of expressed sequence tags (ESTs) has been generated from tissue-specific normalised libraries. In addition, bacterial artificial chromosome (BAC) libraries are being constructed, and information on the genome structure and size from different species has been obtained. An international consortium is now in place to further efforts to lead to a full genome project.
13094 Cabrero, P., Pollock, V.P., Davies, S.A. & Dow, J.A.T., 2004. A conserved domain of alkaline phosphatase expression in the Malpighian tubules of dipteran insects. Journal of Experimental Biology, 207 (19): 3299 - 3305.
Dow: Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 6NU, UK. [j.a.t.dow@ bio.gla.ac.uk]
Malpighian (renal) tubules are key components of the insect osmoregulatory system and show correspondingly great diversity in both number and length. Recently, the organization of the Drosophila melanogaster tubule has been elucidated by enhancer trapping, and a gene expression array for functional properties has been shown to align with the functional domains. In Drosophila, there is a lower tubule domain, which coincides with expression of alkaline phosphatase and delineates the absorptive region of the tubule. Here, these observations are extended to three dipteran disease vectors (Aedes aegypti, Anopheles stephensi and Glossina morsitans) and a non-dipteran out-group, Schistocerca gregaria. Despite a huge range in cell number and size, alkaline phosphatase was found on the apical surface of the lower 10 percent of each of the dipteran tubules but nowhere within the orthopteran tubule. An alkaline phosphatase lower tubule domain is thus conserved among Diptera. Cell counts were also provided for each species. As in Drosophila, stellate cells were not found in the lower tubule domain of Anopheles or Aedes tubules, confirming the unique genetic identity of this domain. As previously reported, we failed to find stellate cells in Schistocerca but, remarkably, also failed to find them in Glossina, the dipteran most closely related to Drosophila. The orthodoxy that stellate cells are unique to, and general among, Diptera may thus require revision.
13095 Dale, C., Jones, T. & Pontes, M., 2005. Degenerative evolution and functional diversification of type-III secretion systems in the insect endosymbiont Sodalis glossinidius. Molecular Biology and Evolution, 22 (3): 758 - 766.
Dale: Department of Biology, University of Utah, Salt Lake City, USA. [[email protected]]
Sodalis glossinidius, a maternally transmitted endosymbiont of tsetse flies, maintains two phylogenetically distinct type-III secretion systems encoded by chromosomal symbiosis regions designated SSR-1 and SSR-2. Although both symbiosis regions are closely related to extant pathogenicity islands with similar gene inventories, SSR-2 has undergone novel degenerative adaptations in the transition to mutualism. Notably, SSR-2 lacks homologues of genes found in SSR-1 that encode secreted effector proteins known to facilitate the host cell cytoskeletal rearrangements necessary for bacterial entry and uptake into eukaryotic cells. Also, as a result of relaxed selection, SSR-2 has undergone inactivation of genes encoding components of the type-III secretion system needle substructure. In the current study, we used quantitative PCR to determine the expression profiles of ysaV (SSR-1) and invA (SSR-2) transcripts when S. glossinidius infects an insect cell line, and we used an invasion assay to characterise the phenotype of an S. glossinidius mutant that lacks the ability to produce an OrgA protein that is required for function of the SSR-2 secretome. Whereas SSR-1 is required for bacterial invasion of host cells and ysaV is expressed when bacteria contact host cells, SSR-2 is required for bacterial proliferation after entry, and invA is only expressed in the intracellular stage of infection. These results demonstrate that degenerative genetic adaptations in SSR-2 have promoted functional diversification of the Sodalis SSR-2 type-III secretion system.
13096 Dinglasan, R.R., Valenzuela, J.G. & Azad, A.F., 2005. Sugar epitopes as potential universal disease transmission blocking targets. Insect Biochemistry and Molecular Biology, 35 (1): 1 - 10.
Dinglasan: Department of Microbiology and Immunology, University of Maryland School of Medicine, 20 Penn Street, Baltimore, MD 21201, USA.
One promising method to prevent vector-borne diseases is through the use of transmission blocking vaccines (TBVs). However, developing several anti-pathogen TBVs may be impractical. In this study, we have identified a conserved candidate carbohydrate target in the midguts of several arthropod vectors. Tests suggested that the anticarbohydrate malaria transmission blocking monoclonal antibody (MG96) preferentially recognises a particular discontinuous glycotope on arthropod vector midguts. The data suggest that these glycotopes may represent potential transmission blocking vaccine targets for a wide range of vector-borne pathogens.
13097 Gooding, R.H. & Krafsur, E.S., 2005. Tsetse genetics: Contributions to biology, systematics, and control of tsetse flies. Annual Review of Entomology, 50: 101 - 123.
Gooding: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
This review covers the distribution and importance of tsetse flies; the tsetse life cycle; population biology; the status of tsetse genetics; genetic variation; linkage groups; sex determination; population genetics; systematics and genetic methods of population suppression. In conclusion, it is mentioned that our knowledge of the genetics of tsetse greatly lags behind that of the pathogenic organism Trypanosoma.
13098 Gooding, R.H., Solano, P. & Ravel, S., 2004. X-chromosome mapping experiments suggest occurrence of cryptic species in the tsetse fly Glossina palpalis palpalis. Canadian Journal of Zoology - Revue Canadienne de Zoologie, 82 (12): 1902 - 1909.
Gooding: Univ Alberta, Department of Biological Sciences, University of Alberts, Edmonton, AB T6G 2E9, Canada.
Using flies from colonies of Glossina palpalis palpalis that originated in Nigeria and Bas-Zaire, the two microsatellite loci Gpg19.62 and Gpg55.3 have been added to the X-chromosome map, thus increasing to seven the number of loci mapped on that chromosome. During the mapping and other crossing experiments, sterile F1 and backcross males were found. Similarities between the patterns of sterility found in the present study and those occurring during hybridization of some subspecies of tsetse suggest that the nominal taxon G. p. palpalis may contain cryptic taxa. Differences in the width of the postgonite head in the genitalia of males from the two colonies were consistent with this suggestion.
13099 Hens, K., Macours, N., Claeys, I., Francis, C. & Huybrechts, R., 2004. Cloning and expression of the yolk protein of the tsetse fly Glossina morsitans morsitans. Insect Biochemistry and Molecular Biology, 34 (12): 1281 - 1287.
Hens: Department of Biology, Catholic University of Leuven, Naamsestraat 59, 3000 Leuven, Belgium.
Two major families of nutritional proteins exist in insects, namely the vitellogenins and the yolk proteins. While in other insects only vitellogenins are found, cyclorraphan flies only contain yolk proteins. Possible sites of yolk protein synthesis are the fat body and the follicle cells surrounding the oocyte. We report the cloning of the yolk protein of the tsetse fly Glossina morsitans morsitans, a species with adenotrophic viviparity. The tsetse fly yolk protein could be aligned with other dipteran yolk proteins and with some vertebrate lipases. In contrast to the situation in most fly species, only a single yolk protein gene was found in the tsetse fly. Northern blot analysis showed that only the ovarian follicle cells, and not the fat body, represent the site of yolk protein synthesis.
13100 Hu, Y.J. & Aksoy, S., 2005. An antimicrobial peptide with trypanocidal activity characterised from Glossina morsitans morsitans. Insect Biochemistry and Molecular Biology, 35 (2): 105 - 115.
Aksoy: Department of Epidemiology and Public Health, Section of Vector Biology, Yale University, School of Medicine, 60 College St., 606 LEPH, New Haven, CT 06510, USA
Tsetse flies are vectors of African trypanosomes, the protozoan agents of devastating diseases in humans and animals. Prior studies in trypanosome infected Glossina morsitans morsitans have shown induced expression and synthesis of several antimicrobial peptides in fat body tissue. Here, we have expressed one of these peptides, Attacin (GmAttA1) in Drosophila (S2) cells in vitro. We show that the purified recombinant protein (recGmAttA1) has strong antimicrobial activity against Escherichia coli-K12, but not against the enteric gram-negative symbiont of tsetse, Sodalis glossinidius. The recGmAttA1 also demonstrated inhibitory effects against both the mammalian bloodstream form and the insect stage Trypanosoma brucei in vitro (minimal inhibitory concentration MIC50 0.075 ìM). When blood meals were supplemented with purified recGmAttA1 during the course of parasite infection, the prevalence of trypanosome infections in tsetse midgut was significantly reduced. Feeding fertile females GmAttA1 did not affect the fecundity or the longevity of mothers, nor did it affect the hatchability of their offspring. We discuss a paratransgenic strategy, which involves the expression of trypanocidal molecules such as recGmAttA1 in the midgut symbiont Sodalis in vivo to reduce trypanosome transmission.
13101 Manosree Chandra, Liniger, M., Tetley, L., Roditi, I. & Barry, J.D., 2004. TsetseEP, a gut protein from the tsetse Glossina morsitans, is related to a major surface glycoprotein of trypanosomes transmitted by the fly and to the products of a Drosophila gene family. Insect Biochemistry and Molecular Biology, 34 (11): 1163 - 1173.
Barry: Wellcome Centre for Molecular Parasitology, University of Glasgow, 56 Dumbarton Road, Glasgow G11 6NU, UK.
African trypanosomes live in the lumen of the gut of tsetse (Glossina) and may have to face an immune response. As yet, it is unclear whether they are sensitive to antimicrobial peptides in vivo, but for some years there has been indirect evidence that one or more lectins can influence the infection. We have purified a protein complex from midgut extracts that, by SDS-PAGE, is a doublet of 37 and 38 kDa in a ratio of 3:1. Through prediction from corresponding cDNA clones, the full-length protein (tsetseEP) contains 320 amino acids, including a signal peptide. There is apparently only one gene encoding this protein. Towards the C terminus, the protein contains a run of 59 (EP) repeats, which surprisingly is what comprises almost the entire mature EP procyclin molecule present on the surface of trypanosomes in the tsetse gut. Drosophila contains a number of genes encoding proteins, of unknown function, with the same cysteine pattern as tsetseEP; this pattern is not reported for any other protein. Immunoblotting with a monoclonal antibody against (EP) repeats reveals expression in the gut, but not salivary glands, of female and male flies, whether or not fed. Immunoelectron microscopy shows the presence in vesicles in midgut cells and in the lumen of the gut. Attempts to demonstrate lectin activity were thwarted by limited availability of the protein complex.
13102 Pollock, V.P., McGettigan, J., Cabrero, P., Maudlin, I.M., Dow, J.A.T. & Davies, S.A., 2004. Conservation of capa peptide-induced nitric oxide signalling in Diptera. Journal of Experimental Biology, 207 (23): 4135 - 4145.
Davies: Institute of Biomedical and Life Sciences, Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, UK. [[email protected]]
In Drosophila melanogaster Malpighian (renal) tubules, the capa peptides stimulate the production of nitric oxide (NO) and guanosine 3?, 5?-cyclic monophosphate (cGMP), resulting in increased fluid transport. The roles of NO synthase (NOS), NO and cGMP in capa peptide signalling were tested in several other insect species of medical relevance within the Diptera (Aedes aegypti, Anopheles stephensi and Glossina morsitans) and in one orthopteran out-group, Schistocerca gregaria. NOS immunoreactivity was detectable by immunocytochemistry in tubules from all species studied. Drosophila melanogaster, Ae. aegypti and An. stephensi only expressed NOS in the principal cells, whereas G. morsitans and S. gregaria showed a general NOS expression in the tubule. Measurement of associated NOS activity (NADPH diaphorase) showed that both D. melanogaster capa-1 and the 2 capa peptides encoded in the An. gambiae genome, QGLVPFPRVamide (AngCAPA-QGL) and GPTVGLFAFPRVamide (AngCAPA-GPT), all stimulated NOS activity in D. melanogaster, Ae. aegypti, An. stephensi and G. morsitans tubules but not in S. gregaria. Furthermore, capa-stimulated NOS activity in all the Diptera was inhibited by the NOS inhibitor L-NAME. All capa peptides stimulated an increase in cGMP content across the dipteran species, but not in S. gregaria. Similarly, all capa peptides tested stimulated the fluid secretion in D. melanogaster, Ae. aegypti, An. stephensi and G. morsitans tubules, but had either no effect or were inhibitory on S. gregaria. Consistent with these results, the Drosophila capa receptor was shown to be expressed in Drosophila tubules, and its closest Anopheles homologue was shown to be expressed in Anopheles tubules. This was the first demonstration of the physiological roles of two putative An. gambiae neuropeptides. We also demonstrated neuropeptide modulation of fluid secretion in tsetse tubule for the first time. Finally, we show the generality of capa peptide action, to stimulate NO/cGMP signalling and increase fluid transport, across the Diptera, but not in an orthopteran.
[See also 28: 13097]
13103 Barrozo, R., Schilman P., Minoli, S. & Lazzari, C., 2004. Daily rhythms in disease-vector insects. Biological Rhythm Research, 35 (1 - 2): 79 - 92.
Barrozo: Laboratorio de Fisiología de Insectos, DBBE, Facultad de Ciencias, Exactas y Naturales Universidad de Buenos Aires, Argentina
The host-vector-parasite interaction offers a clear illustration of the adaptive value of biological rhythms. In this review, we summarise some of the information currently available on daily rhythms of insect vectors, particularly those responsible for the transmission of parasites to humans. Included amongst the cases described are circadian rhythms of locomotor and flight activity, and of eclosion and oviposition in tsetse flies, blood-sucking hemipterans, mosquitoes and other haematophagous insects. Both published and new data are presented, and they indicate that a study of the rhythms in disease-vector insects can provide an understanding of the value of this application of chronobiology to ecology and applied sciences. Related to this, the possibility of strategies for the control of insects based on their temporal characteristics is proposed; for example, the use of insecticides could be restricted to those phases of the day when the susceptibility of the insects to them is increased.
13104 Dankwa, D., Oddoye, E.O.K. & Mzamo, K.B., 2000. Efficacy of three trap types for trapping Glossina palpalis, G. tachinoides, and G. mortisans in the Mole Game Reserve in Ghana. Ghana Journal of Agricultural Science, 33 (2): 177 - 181.
Dankwa: Animal Research Institute, Council for Scientific and Industrial Research, P. O. Box AH 20, Achimota, Ghana.
A study was undertaken to determine the most effective of three trap types (biconical, monoconical, and NGU Siamese (NG2B)) for catching three Glossina species (G. palpalis, G. tachinoides, and G. mortisans). The three species were trapped in the Mole Game Reserve. Results showed that in the absence of odour attractants, the biconical trap was the most efficient trap. Out of a total of 4 619 tsetse flies caught during the trapping period, 2 073 (44.9 percent) were caught in the biconical trap. The monoconical trap caught 1 362 tsetse flies (29.5 percent) whilst the NG2B trap caught 1 184 tsetse flies (25.6 percent). There were, however, locational differences, with the number of flies caught in the riverine area being significantly higher than the number caught in the pond area, but not significantly different from the number caught in the woodland. There was also a very significant difference in the species of tsetse flies caught by the traps. Significantly more G. tachinoides were caught as compared to G. mortisans; virtually no G. palpalis were caught. The number of female flies caught (3 621) was significantly higher than the number of male flies caught (995).
13105 Geerts, S., Mahama, C.I., Kone, A., de la Rocque, S., & De Deken, R. 2005. Prediction of the distribution of Glossina tachinoides (Diptera: Glossinidae) in the Volta basin of northern Ghana. Bulletin of Entomological Research, 95 (1): 63 - 67.
Geerts: Animal Health Department, Institute of Tropical Medicine, Nationalestraat 155, B-2000, Antwerp, Belgium.
The classification of a Landsat Thematic Mapper satellite image helped demonstrate prevailing habitat types and land use intensity in the Volta basin of the Northern Region of Ghana. A geo-referenced data layer comprising the capture results of a cross-sectional survey of Glossina tachinoides was overlaid on a data layer of habitat types within 500m of either bank of the Volta River and its tributaries. An evaluation of the relationship between habitat types and the capture results of G. tachinoides suggested a strong preference of G. tachinoides for woodland, followed by shrubland, grassland and flood plains. The findings were used to classify the suitability of habitat types for G. tachinoides as ‘high’, ‘medium’ and ‘low’ and a prediction map for the distribution of G. tachinoides in the entire river network was produced. The usefulness of this method in estimating the potential distribution of G. tachinoides in an area of increasing agricultural expansion is discussed.
13106 Getachew Abebe, Malone, J.B. & Thompson, A.R., 2004. Geospatial forecast model for tsetse-transmitted animal trypanosomosis in Ethiopia. SINET: Ethiopian Journal of Science, 27 (1): 1 - 8.
Thompson: Faculty of Veterinary Medicine, Addis Ababa University, PO Box 34, Debre Zeit, Ethiopia.
The aims of this study were to develop a geographic information system (GIS) forecast and risk assessment model for cyclically transmitted trypanosomosis in Ethiopia by matching features in the environment to available information on the preferences and limits of tolerance of the parasite and its vector, and validate and further develop the GIS model using data from current and historical prevalence survey data and habitat microenvironment studies from trypanosomosis endemic areas. Results indicate that a GIS model developed for parasitic diseases based on the growing degree day (GDD) concept can be applied to tsetse-transmitted trypanosomosis. These GIS for animal trypanosomosis were created using Food and Agriculture Organization-Crop Production System Zones (FAO-CPSZ) database and Normalised Difference Vegetation Index (NDVI) and maximum temperature (Tmax) from the Global Land 1 km dataset. The two datasets used to determine the risk of tsetse flies and consequently animal trypanosomosis in Ethiopia indicated the magnitude of the disease and possible expansion of the "fly belt" in the future. The GIS model indicated the distribution and importance of tsetse-transmitted trypanosomosis in Ethiopia. Spatial and statistical analyses verified the use of the GDD concept and climate forecast system that were developed to determine the suitability of a given environment for the proliferation of a biotype, in this case tsetse and trypanosomes. Results presented here indicate the importance of GDD and the two climatic variables (NDVI and Tmax) in the development of a forecast model for tsetse-transmitted trypanosomosis in Ethiopia.
13107 Marquez, J.G., Vreysen, M.J.B., Robinson, A.S., Bado, S. & Krafsur, E.S., 2004. Mitochondrial diversity analysis of Glossina palpalis gambiensis from Mali and Senegal. Medical and Veterinary Entomology, 18 (3): 288 - 295.
Krafsur: Department of Entomology, Iowa State University, Ames, IA 50011, USA.
West African riverine tsetse populations of Glossina palpalis gambiensis were investigated for gene flow, inferred from mitochondrial diversity in samples of 69 flies from Senegal and 303 flies from three river drainages in Mali. Four polymorphic mitochondrial loci were scored. Mean haplotype diversities were 0.30 in Mali, 0 in Senegal and 0.18 over both Mali and Senegal. These diversities estimate the probabilities that two randomly chosen tsetse have different haplotypes. Substantial rates of gene flow were detected among flies sampled along tributaries belonging to the river basins of the Senegal, Niger, and Bani in Mali. There was virtually no gene flow between tsetse in Senegal and Mali. No seasonal effects on gene flow were detected. The implications of these preliminary findings for the implementation of area-wide integrated pest management (AW-IPM) programmes against riverine tsetse in West Africa are discussed.
[See also 28: 13091, 13097]
13108 Admassu, B., Nega, S., Haile, T., Abera, B., Hussein, A. & Catley, A., 2005. Impact assessment of a community-based animal health project in Dollo Ado and Dollo Bay Districts, Southern Ethiopia. Tropical Animal Health and Production, 37 (1): 33 - 48.
Catley: African Union/Interafrican Bureau for Animal Resources, PO Box 30786, 00100 Nairobi, Kenya.
Participatory methods were used to assess the impact of a community-based animal health worker (CAHW) project in two remote pastoralist districts of Ethiopia. The CAHW project had been operating for three years at the time of the assessment. Participatory methods were standardised and repeated with ten groups of informants in the project area. The assessment showed significant reductions in disease impact for diseases handled by CAHWs compared with diseases not handled by CAHWs. In camels, there was significant reduction in the impact of mange, trypanosomosis, helminthosis, anthrax and non-specific respiratory disease. In cattle there was a significant reduction in the impact of blackleg, anthrax and helminthosis. In sheep and goats there was a significant reduction in the impact of mange, helminthosis, contagious caprine pleuropneumonia, orf and non-specific diarrhoea. In order of importance, these reductions in disease impact were attributed to (1) increased use of modern veterinary services provided by CAHWs, (2) vaccination campaigns involving CAHWs, (3) good rainfall and availability of grazing and (4) decreased herd mobility. Decreased herd mobility was also associated with negative impact of tick infestation. Community-based animal health workers were considered to be highly accessible, available, affordable and trustworthy relative to other service providers. They were also perceived to be suppliers of a good quality service. Specific types of positive impact attributed to CAHW activities were increases in milk, meat, income and draught power.
13109 Barclay, H.J. & Hargrove, J.W., 2005. Probability models to facilitate a declaration of pest-free status, with special reference to tsetse (Diptera: Glossinidae). Bulletin of Entomological Research, 95 (1): 1 - 11.
Barclay: Pacific Forestry Centre, 506 West Burnside Road, Victoria, British Columbia V8Z 1M5, Canada.
A methodology is presented to facilitate a declaration that an area is ‘pest-free’ following an eradication campaign against an insect pest. This involves probability models to assess null trapping results and also growth models to help verify, following a waiting period, that pests were not present when control was stopped. Two probability models are developed to calculate the probability of negative trapping results if in fact insects were present. If this probability is sufficiently low, then the hypothesis that insects are present is rejected. The models depend on knowledge of the efficiency and the area of attractiveness of the traps. To verify the results of the probability model, a waiting period is required to see if a rebound occurs. If an incipient but non-detectable population remains after control measures are discontinued, then a rebound should occur. Using a growth model, the rate of increase of an insect population is examined starting from one gravid female or one male and a female. An example is given for tsetse in which both means and confidence limits are calculated for a period of 24 reproductive periods after control is terminated. If no rebound is detected, then a declaration of eradication can be made.
13110 De Deken, R., Speybroeck, N., Gillain, G., Sigue, H., Batawi, K. & Van den Bossche, P., 2004. The macrocyclic lactone "spinosad", a promising insecticide for tsetse fly control. Journal of Medical Entomology, 41 (5): 814 - 818.
De Deken: Veterinary Department, Institute of Tropical Medicine, Nationalestraat 155, B-2000, Antwerp, Belgium.
The susceptibility of tsetse flies, Glossina palpalis gambiensis, and G. m. morsitans to topically applied spinosad, a mixture of insecticidal molecules from the actinomycete Saccharopolyspora spinosa, is almost as high as to deltamethrin. However, susceptibility to spinosad does not differ significantly between teneral and gravid flies, contrary to the reaction to deltamethrin. Spinosad might be a promising candidate for future tsetse control by the sequential aerial technique.
13111 Foil, L.D., Coleman, P., Eisler, M., Fragoso-Sanchez, H., Garcia-Vazquez, Z., Guerrero, F.D., Jonsson, N.N., Langstaff, I.G., Li, A.Y., Machila, N., Miller, R.J., Morton, J., Pruett, J.H. & Torr, S., 2004. Factors that influence the prevalence of acaricide resistance and tick-borne diseases. Veterinary Parasitology, 125 (1 - 2): 163 - 181.
Foil: Entomology Department, 402 Life Sciences Building, Louisiana State University Agricultural Center, Baton Rouge, LA 70803, USA.
Within a broader survey, this review of acaricide resistance mentions that the use of pesticides for the control of pests of cattle other than ticks can affect the incidence of tick resistance and tick-borne diseases. Simple analytical models of tick- and tsetse-borne diseases suggest that reducing the abundance of ticks, for example by treating cattle with pyrethroids, can have a variety of effects on tick-borne diseases. In the worst-case scenario, the models suggest that treating cattle might not only have no impact on trypanosomosis but could increase the incidence of tick-borne disease. In the best-case scenario, treatment could reduce the incidence of both trypanosomosis and tick-borne diseases.
13112 Habtewold, T., Prior, A., Torr, S.J. & Gibson, G., 2004. Could insecticide-treated cattle reduce Afrotropical malaria transmission? Effects of deltamethrin-treated Zebu on Anopheles arabiensis behaviour and survival in Ethiopia. Medical and Veterinary Entomology, 18 (4): 408 - 417.
Gibson: FARM-Africa, Southampton Place, London, UK.
Anopheles arabiensis is the most widespread vector of malaria in the Afrotropical Region. Because An. arabiensis feeds readily on cattle as well as humans, the insecticide-treatment of cattle as employed to control tsetse and ticks might simultaneously affect the malaria vectorial capacity of this mosquito. Field experiments in southern Ethiopia were conducted to establish whether Zebu cattle treated with a pour-on pyrethroid formulation of 1 percent deltamethrin, widely used to control ticks and tsetse, would be effective against An. arabiensis or cause the female mosquitoes to feed more frequently on humans due to behavioural avoidance of insecticide-treated cattle. Contact bioassays (3 min exposure) showed that the insecticide remained effective for about 1 month (kill rate > 50 percent) against mosquitoes feeding on the flanks of treated cattle. A novel behavioural assay demonstrated that An. arabiensis readily fed on insecticide-treated cattle and were not deflected to human hosts in the presence of treated cattle. DNA-fingerprinting of bloodmeals revealed that in nature An. arabiensis feeds most frequently on older animals, coinciding with the established practice of applying insecticide only to older cattle, in order to allow younger untreated animals to gain immunity against infections transmitted by ticks. These encouraging results were tempered by finding that >90 percent of An. arabiensis, An. pharoensis and An. tenebrosus females feed on the legs of cattle, farthest from the site of pour-on application along the animal’s back and where the treatment may be least residual due to weathering. Observations of mosquitoes feeding naturally on insecticide-treated cattle showed that the majority of wild female anophelines alighted on the host animal for less than 1 min to feed, with significantly shorter mean duration of feeding bouts on insecticide-treated animals, and the effective life of the insecticide was only 1 week. Thus the monthly application of deltamethrin to cattle, typically used to control tsetse and ticks, is unlikely to be effective against An. arabiensis populations or their vectorial capacity. Even so, it seems likely that far greater impact on anopheline mosquitoes could be achieved by applying insecticide selectively to the legs of cattle.
13113 Hargrove, J.W., 2005. Extinction probabilities and times to extinction for populations of tsetse flies Glossina spp. (Diptera: Glossinidae) subjected to various control measures. Bulletin of Entomological Research, 95 (1): 13 - 21.
Hargrove: 9 Monmouth Rd, Avondale, Harare, Zimbabwe
A stochastic branching process was used to derive equations for the mean and variance of the probability of, and time to, extinction in tsetse populations. If the remnant population is a single inseminated female, the extinction probability increases linearly with adult mortality and is always certain if this mortality >3.5 percent per day even for zero pupal mortality. If the latter mortality is 4 percent per day, certain extinction is only avoided if adult mortality <1.5 percent per day. For remnant female populations >1, the extinction probability increases in a non-linear manner with adult mortality. Extinction is still certain for adult mortality >3.5 percent per day but, when the remnant population is >16, extinction is highly unlikely for adult mortality <2.5 percent per day if all females are inseminated. Extinction probability increases with increasing probability of sterile mating in much the same way as it does with increasing adult mortality. Extinction is assured if the probability of insemination can be reduced to 0.1. The required reduction decreases with increasing adult mortality. For adult mortality equal to 6 - 8 percent per day, the time to extinction increases only by one generation per order of magnitude increase in the starting population. Time to extinction is less sensitive to changes in the pupal than in the adult mortality. Reductions in the probability of insemination only become important when adult mortality is small; if the adult mortality is 8 percent per day, reducing the insemination probability from 1 to 0.1 only reduces the expected time to extinction by two generations. Conversely, increases in adult mortality produce important reductions in the required time even when the probability of insemination is 0.1. The practical, economic implication for the sterile insect technique is that the low-tech methods used to suppress tsetse populations should not be halted when the release of sterile males is initiated. The sterile insect technique should only be contemplated when it has been demonstrated that the low-tech methods have failed to effect eradication. The theory is shown to be in good accord with the observed results of tsetse control campaigns involving the use of odour-baited targets in Zimbabwe and the sterile insect technique on Unguja Island, Zanzibar.
13114 Muriuki, G.W., Njoka, T.J., Reid, R.S. & Nyariki, D.M., 2005. Tsetse control and land-use change in Lambwe valley, south-western Kenya. Agriculture Ecosystems and Environment, 106 (1): 99 - 107.
Muriuki: Kenya Trypanosomiasis Research Institute, PO Box 362, Kikuyu, Kenya.
For a long time, trypanosomosis spread by the tsetse fly constrained human settlement in the Lambwe Valley, a south-western Kenya rangeland. After lengthy efforts to control tsetse over many years, the valley is currently experiencing an increase in human population growth rate, and rapid changes in land-use and cover are taking place. Using time-series aerial photograph interpretation, social survey methods, and a review of human population trends over five decades, a three-fold expansion in cultivation in the settled areas over a 50-year period, with a consequent decrease in woody vegetation cover was identified. In the Ruma National Park, occupying a third of the valley floor, shrublands and thickets have expanded while open grasslands have decreased. The sudden increase of land under cultivation adjacent to prime agricultural land designated for wildlife conservation, exacerbated by bush encroachment and dwindling resources for tsetse control could provide a situation suitable for land-use conflicts. Sustainability of this unique rangeland is dependent on how judiciously the resources are shared among all stakeholders in the valley. This study suggests continued tsetse surveillance and agricultural intensification in the settled areas to minimise chances of conflicts in land-use.
13115 Otim, C.P., Ocaido, M., Okuna, N.M., Erume, J., Ssekitto, C., Wafula, R.Z.O., Kakaire, D., Walubengo, J., Okello, A., Mugisha, A. & Monrad, J., 2004. Disease and vector constraints affecting cattle production in pastoral communities of Ssembabule district, Uganda. Livestock Research for Rural Development, 16 (5): article 35.
Monrad: Royal Veterinary and Agricultural University, Dyrlaegevej 100, DK-1870 Frederiksberg C, Denmark. [[email protected]]
A survey was carried out to determine the disease and vector constraints to cattle production in pastoral communities settled in three villages of two sub-counties in Ssembabule district, Uganda. A total of 454 cattle randomly selected were sampled for blood parasite infections (antibody ELISA serology and direct parasite detection), for gastrointestinal parasites and for tick infestation. Tsetse exposure was assessed by trapping. The prevalence of trypanosomiasis was low on direct trypanosome detection in blood samples (0.7 percent) as well as on serology (6.7 percent), and no tsetse flies were encountered. Three head of cattle (0.7 percent) were infected with Theileria parva, the cause of East Coast Fever (ECF). However, serological analysis for antibodies against Theileria parva revealed a very high prevalence of exposed animals (93.3 percent). Three head of cattle (0.7 percent) were further found infected with Anaplasma marginale. In addition, 59.1 percent of the cattle examined were shedding worm eggs. Meanwhile 28.7 percent of the sera of cattle tested using Rose Bengal rapid agglutination test were positive for bovine brucellosis. A relatively high tick infestation was demonstrated. Rhipicephalus appendiculatus was found to be the most abundant species, followed by R. evertsi and Amblyomma variegatum. In a preceding questionnaire survey the cattle owners in Ssembabule district had pointed to trypanosomiasis as their most important disease problem. This laboratory-based diagnostic survey, however, revealed that ticks, tick-borne diseases and brucellosis were the real major constraints to cattle production in that district, while tsetse and trypanosomiasis appeared to be of little or no importance. It is concluded that planning of disease control measures in a given area should depend on laboratory-based diagnostic observations rather than on a questionnaire survey.
[See also 28: 13100, 13132, 13147, 13149]
13116 Abenga, J.N. & Lawal, I.A., 2005. Implicating roles of animal reservoir hosts in the resurgence of Gambian trypanosomosis (sleeping sickness). African Journal of Biotechnology, 4 (2): 134 - 137.
Abenga: Pathology, Epidemiology and Statistics Division, Nigerian Institute for Trypanosomiasis Research, PMB 2077, Kaduna, Kaduna State, Nigeria. [[email protected]]
Gambian trypanosomosis is a complex and debilitating disease of man. For many years the disease has been ravaging several parts of sub-Saharan Africa despite decades of therapeutic control. Although animal reservoir hosts are believed to be associated with the disease, not much evidence has been brought forward to prove the existence of animal reservoir hosts for Trypanosoma brucei gambiense and the zoonotic nature of Gambian sleeping sickness. This paper reviews recent evidence based on molecular and other biotechnologies leading to the identification of mammalian hosts as reservoirs of T. b. gambiense and the roles of such hosts in the transmission and resurgence of sleeping sickness in sub-Saharan Africa.
13117 Chiejina, S.N., Musongong, G.A., Fakae, B.B., Behnke, J.M., Ngongeh, L.A. & Wakelin, D., 2005. The modulatory influence of Trypanosoma brucei on challenge infection with Haemonchus contortus in Nigerian West African Dwarf goats segregated into weak and strong responders to the nematode. Veterinary Parasitology, 128 (1 - 2): 29 - 40.
Behnke: School of Biology, University of Nottingham, Nottingham NG7 2RD, UK
Although Nigerian West African Dwarf (WAD) goats are relatively resistant to infection with Haemonchus contortus and are also trypanotolerant, natural outbreaks of both infections are known to occur. Despite their relative resistance to H. contortus WAD goats nevertheless show variability in response phenotype and it was of interest to examine the effect of this variability on the outcome of concurrent trypanosome infection. Trypanosoma brucei infections were established in goats that were initially classified as good or poor responders to H. contortus. Thirty-nine goats were exposed to an escalating infection with H. contortus, and on the basis of their mean faecal egg counts (FEC) were allocated to high FEC (poor responders, 18 goats with the highest FEC) or low FEC (good responders, 18 goats with the lowest FEC) classes. Nine uninfected naïve control goats were included to provide reference baseline values. Retrospective analysis of parasitological and pathological parameters after allocation into high/low FEC classes showed that FECs differed significantly, in both classes packed cell volume (PCV) values fell relative to naïve controls, neither class lost weight and both generated marked IgG responses. All goats received anthelminthic on day 61, half of each group was infected with 50 million trypanosomes and on day 67, excepting the controls, all goats were challenged with 3000 L3 of H. contortus. Trypanosome parasitaemia was generally low, and marginally, but not significantly, higher in the low compared with high FEC class, peaking 12 - 16 days after exposure in both groups and then falling to below microscopically detectable levels (although still detectable by sub-inoculation into mice) by week 3. At autopsy (days 109 - 110), worm burdens were significantly higher in the trypanosome-infected goats from the high FEC class, relative to all other groups. Trypanosome infected goats showed a tendency (although not significant) towards higher FEC and, irrespective of their FEC class, had lower PCV values although body weight did not vary significantly. All goats challenged with H. contortus had higher antibody levels than naïve controls, but neither trypanosome infection nor FEC class affected the magnitude of responses. These results confirm that WAD goats comprise a range of response phenotypes to initial H. contortus infection and that trypanotolerance is a key trait of this breed. Although immunity to nematode infection develops even in poor responders, these animals harbour higher nematode burdens during concurrent infection with T. brucei.
13118 Chretien, J.-P.L. & Smoak, B.L., 2005. African trypanosomiasis: changing epidemiology and consequences. Current Infectious Disease Reports, 7 (1): 54 - 60.
Chretien: Department of Defense Global Emerging Infections Surveillance & Response System (DoD-GEIS), Division of Preventive Medicine, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Human African trypanosomiasis has re-emerged as a serious public health threat after near-elimination because of diminished investment in previously successful control programs. The continued, occasional importation of African trypanosomiasis to the United States can be expected as tourists and immigrants travel from high-risk areas. No vaccine or chemoprophylaxis is available for this disease, and travellers to affected areas should be counselled on tsetse fly avoidance. New diagnostic and staging tests are promising but have not replaced the classical method of examining body fluids for trypanosomes. Prompt diagnosis and staging is essential because if untreated, East African and West African sleeping sickness are fatal. Drug regimens are toxic and cumbersome, and short-term prospects for therapeutic advances are limited.
13119 Courtin, F., Dupont, S., Zeze, D.G., Jamonneau, V., Sané, B., Coulibaly, B., Cuny, G. & Solano, P., 2005. Trypanosomose Humaine Africaine: transmission urbaine dans le foyer de Bonon (Côte d’Ivoire). [Human African trypanosomiasis: urban transmission in the Bonon (Côte d’Ivoire) focus.] Tropical Medicine and International Health, 10 (4): 340 - 346.
Solano: Institut Pierre Richet, Rue Fleming zone 4C, Abidjan 04, Côte d’Ivoire.
Human African trypanosomiasis (HAT) is a vector-borne parasitic disease which has often been considered a rural disease. Population increases in African countries have entailed the spread of urban centres, creating favourable conditions for the appearance of new epidemiological conditions. In Côte d’Ivoire, HAT transmission has been described in the surroundings of towns such as Daloa or Sinfra. In the focus of Bonon, located in central-western Côte d’Ivoire, a medical survey detected 96 patients. The sites visited by the patients every day were geo-referenced and the routes between them recorded. In parallel, an entomological survey of the patients’ daily locations enabled the collection of data on the vector. In Bonon, we observed urban cases and tsetse (Glossina palpalis) feeding on people. Trypanosoma brucei gambiense was identified in both man and vector; thus all conditions for possible intra-urban trypanosomosis transmission were met. The consequences of this are discussed regarding the problem of diffusion of the disease.
13120 Grébaut, P., Mbida, J.A.M., Kondjio, C.A., Njiokou, F., Penchenier, L. & Laveissière, C., 2004. Spatial and temporal patterns of human African trypanosomosis (HAT) transmission risk in the Bipindi focus, in the forest zone of Southern Cameroon. Vector Borne and Zoonotic Diseases, 4 (3): 230 - 238.
Grébaut: Laboratoire de Recherche et de Coordination contre les Trypanosomoses (LRCT) CIRAD-IRD, Montpellier, France.
Vector control is an effective and cost-efficient way to disrupt the transmission of human African trypanosomosis (HAT); it has nonetheless been little used to date in the disease foci. With the aim to target trapping more precisely and to develop an optimised vector control system, a transmission risk index was used in the HAT focus of Bipindi, in the forest zone of southern Cameroon. The authors used a simplified version of the index originally developed by Laveissière et al. in 1994. The calculation of this new index only requires knowledge of the proportion of teneral flies and the proportion of flies with human blood meals in samples caught in different biotopes. This makes it possible to identify the biotopes displaying permanent risk, such as riverbanks, as well as biotopes displaying seasonal risk, such as marshy hollows and encampments. In the villages, the domestic pig, with 49 percent of the identified blood meals, is the favourite host of the tsetse flies during the short rainy season. The proportion of blood meals taken on human beings does not significantly increase when domestic pigs are absent. Game animals, contributing to 46 percent and 64 percent of the blood meals during the short rainy season and the long dry season, respectively, are also favoured as feeding hosts in this particular HAT focus.
13121 Jamonneau, V., Ravel, S., Koffi, M., Kaba, D., Zeze, D.G., Ndri, L., Sane, B., Coulibaly, B., Cuny, G. & Solano, P., 2004. Mixed infections of trypanosomes in tsetse and pigs and their epidemiological significance in a sleeping sickness focus of Côte d’Ivoire. Parasitology, 129 (6): 693 - 702.
Solano: Institut Pierre Richet, s/c Représentation IRD, Rue Chevalier de Clieu, 15 BP 917, Abidjan 15, France. [[email protected]]
In a sleeping sickness focus of Côte d’Ivoire, trypanosomes were characterised in humans, pigs and tsetse using various techniques. Out of 74 patients, all the 43 stocks isolated by KIVI (Kit for In Vitro Isolation) appeared to belong to only one zymodeme of Trypanosoma brucei gambiense group 1 (the major zymodeme Z3). The only stock isolated on rodents belonged to a different, new, zymodeme (Z50), of T. b. gambiense group 1. From 18 pigs sampled in the same locations as the patients, PCR showed a high proportion of mixed infections of T. brucei s.l. and T. congolense riverine-forest. Zymodemes of T. brucei s.l. from these pigs were different from those found in humans. From a total of 16 260 captured tsetse (Glossina palpalis palpalis), 1 701 were dissected and 28 percent were found to be infected by trypanosomes. The most prevalent trypanosome was T. congolense riverine-forest type, followed by T. vivax, T. brucei s.l. and T. congolense savannah type, this latter being associated with the forest type of T. congolense in most cases. Mixed infections by two or three of these trypanosomes were also found. Use of a microsatellite marker allowed us to distinguish T. b. gambiense group I in some of the mature infections in tsetse. Differences in infection rates and in trypanosome genotypes according to the host might indicate that the pig may not be an active animal reservoir for humans in this focus.
13122 Magona, J.W., Walubengo, J., Odiit, M., Okedi, L.A., Abila, P., Katabazi, B.K., Gidudu, A.M. & Olaho-Mukani, W., 2005. Implications of the re-invasion of Southeast Uganda by Glossina pallidipes on the epidemiology of bovine trypanosomosis. Veterinary Parasitology, 128 (1 - 2): 1 - 9.
Magona: Livestock Health Research Institute, POBox 96, Tororo, Uganda.
A study to assess the influence of re-invasion of Glossina pallidipes on the epidemiology of bovine trypanosomosis was conducted in Southeast Uganda. A total of 1 992 cattle were screened for trypanosomosis in villages using a combination of the BCT and HCT methods; of these cattle, 949 head were in villages infested with G. pallidipes and 1 043 head were in villages without that species. The prevalence of trypanosomosis (15.5 vs 7.1 percent), Trypanosoma brucei infection (1.4 vs 0.6 percent), T. congolense infection (7.2 vs 2.0 percent), T. vivax infection (5.3 vs 3.3 percent) and mixed infection (1.6 vs 1.2 percent) in cattle in villages with G. pallidipes was significantly higher than in those without G. pallidipes. Infections of Trypanosoma congolense were predominant in cattle in villages with G. pallidipes, while T. vivax infections were predominant in cattle in villages without that species. In all villages, T. brucei infections were fewer than either T. congolense or T. vivax infections. The risk of transmission of T. brucei, T. congolense and T. vivax infections was 3, 2.7 and 1.6 times higher, respectively, in villages with G. pallidipes than in those without that species, despite the presence of G. f. fuscipes in both sets of villages. The mean PCV and mean herd size of cattle in villages with G. pallidipes were significantly lower than in those in villages without that species. It is evident that the presence of G. pallidipes brings about an increase in the prevalence of T. congolense, which causes a more severe disease in cattle than other species of trypanosomes. This is a rare case of a re-invasion of a tsetse species, the disease transmission capacity of which calls for a refocusing of the traditional national tsetse and trypanosomosis control strategies to contain it.
13123 Njiokou, F., Simo, G., Nkinin, S.W., Laveissière, C. & Herder, S., 2004. Infection rate of Trypanosoma brucei s.l., T. vivax, T. congolense "forest type", and T. simiae in small wild vertebrates in south Cameroon. Acta Tropica 92 (2): 139 - 146.
Njiokou: LRT, OCEAC, BP 288, Yaounde, Cameroon. [fnjiokou@ yahoo.com]
In order to identify the infection rate of trypanosome species infecting wild animals in four localities (Bipindi, Campo, Fontem and Nditam) of southern Cameroon, 1 141 wild animals were sampled. These animals belonged to 36 species grouped in 8 orders including 407 primates, 347 artiodactyls, 264 rodents, 54 pangolins, 53 small carnivores, 11 saurians and crocodilians and 5 hyraxes. PCR using specific primers for Trypanosoma vivax, T. brucei s.l., T. congolense "forest type" and T. simiae showed that 18.7 percent of the animals were infected by at least one of these trypanosome species. A positive PCR result may not indicate absolutely an active infection because PCR can detect also transient infections. T. vivax (Duttonella) had the highest infection rate (9.5 percent) and was found in almost all the host orders studied. T. brucei s.l. mostly infected primates, rodents and some duikers (Cephalophus dorsalis and C. monticola). Trypanosomes of the subgenus Nannomonas had a lower infection rate of 5.5 percent (2.4 percent for T. simiae and 3.1 percent for T. congolense "forest type"). They were harboured mainly by primates, ungulates and rodents. Trypanosome infection rates were highest in Nditam (24.5 percent) and Bipindi (21 percent). Trypanosoma brucei s.l. (Trypanozoon) had its maximum infection rate of 10.4 percent in Bipindi. The "Quantitative Buffy Coat" (QBC®) and kit for in vitro isolation (KIVI) techniques were used to identify 48 (6.1 percent) infected animals. Thirteen were positive using QBC®), and 42 were positive by KIVI. However, PCR was negative on 16 of these infected animals, probably due to infections with other trypanosome species. This study showed that trypanosomes of the subgenera Duttonella, Nannomonas and Trypanozoon could infect small wild vertebrates as has been shown for large ungulates and carnivores. The presence of T. brucei s.l. in a large range of wild animals strengthens the hypothesis of the existence of a wild animal reservoir of T. b. gambiense in Cameroon.
13124 Turner, C.M.R., McLellan, S., Lindergard, L.A.G., Bisoni, L., Tait, A. & MacLeod, A., 2004. Human infectivity trait in Trypanosoma brucei: stability, heritability and relationship to sra expression. Parasitology, 129 (4): 445 - 454.
Turner: Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK. [[email protected]]
Some Trypanosoma brucei lines infect humans, whereas others do not because the parasites are lysed by human serum. We have developed a robust, quantitative in vitro assay based on differential uptake of fluorescent dyes by live and dead trypanosomes to quantify the extent and kinetics of killing by human serum. This method has been used to discriminate between three classes of human serum resistance: sensitive, resistant and intermediate. TREU 927/4, the parasite used for the T. brucei genome project, is intermediate. The phenotype is expressed in both bloodstream and metacyclic forms, and is stably expressed during chronic infections and on cyclical transmission through tsetse flies. Trypanosomes of intermediate phenotype are distinguished from sensitive populations of cells by the slower rate of lysis and by the potential to become fully resistant to killing by human serum as a result of selection or long-term serial passaging in mice, and to pass on full resistance phenotype to their progeny in a genetic cross. The sra gene has been shown previously to determine human serum resistance in T. brucei but screening for the presence and expression of this gene indicated that it is not responsible for the human serum resistance phenotype in the trypanosome lines that we have examined, indicating that an alternative mechanism for HSR exists in these stocks. Examination of the inheritance of the phenotype in F1 hybrids for both bloodstream and metacyclic stages from two genetic crosses demonstrated that the phenotype is co-inherited in both life-cycle stages in a manner consistent with being a Mendelian trait, determined by only one or a few genes.
[See also 28: 13088, 13118, 13120, 13131]
13125 Agranoff, D., Stich, A., Abel, P. & Krishna, S., 2005. Proteomic fingerprinting for the diagnosis of human African trypanosomiasis. Trends in Parasitology, 21 (4): 154 - 157.
Krishna: Department of Cellular and Molecular Medicine (Infectious Diseases), St George’s Hospital Medical School, Cranmer Terrace, London, SW17 ORE, UK.
Papadopoulos et al. [see TTI 27(2): 12940] recently reported the discovery of a diagnostic serum proteomic signature for human African trypanosomiasis (HAT), using a combination of surface-enhanced laser desorption-ionization time-of-flight (SELDI-TOF) mass spectrometry and data-mining algorithms. This novel approach, coupled with biochemical characterization of the proteins that contribute to the signature, provides powerful new tools for the development of improved diagnostic tests, disease staging and identification of potential novel drug targets in HAT.
13126 Anon. 2005. A new form of human trypanosomiasis in India. Weekly Epidemiological Record, 80 (7): 62 - 63.
Weekly Epidemiological Record: Avenue Appia 20, 1211 Geneva 27, Switzerland.
On 26th October 2004, a 40-year-old farmer working in close contact with livestock in Maharashtra State was admitted to a hospital in Nagpur, India. The patient presented with episodes of fever associated with sensory disorders. Testing of the blood revealed the presence of trypanosomes of Trypanosoma evansi. A specialist from the Institut français de recherche pour le développement (Montpellier, France) was sent by WHO to confirm the parasitological diagnosis. Treatment with suramin over three months led to a rapid improvement. At the time of this report it was assumed that the patient was cured. This is the first formally identified human case in the world of trypanosomiasis caused by T. evansi.
13127 Hutchinson, O.C., Webb, H., Picozzi, K., Welburn, S. & Carrington, M., 2004. Candidate protein selection for diagnostic markers of African trypanosomiasis. Trends in Parasitology, 20 (11): 519 - 523.
Carrington: Institute of Zoology, Zoological Society of London, Regent's Park, London, NW1 4RY, UK.
The ability to accurately diagnose the presence of an infective microorganism is not only important for individual human and animal health and wellbeing, but is also central to surveillance programmes. Effective and sustainable control of many diseases in the developing world depends on the availability of field applicable diagnostics that are cheap, reliable, simple in design and application, and which provide immediate results. This review examines how the genome sequences can be used in the selection of potential candidate proteins for developing new serodiagnostics for African trypanosomiasis.
13128 Ngoma, M.S., Nalubamba, M., Kowa, S., Minyoi, D., Mubanga, J., Mwansa, J., Musuku, J., Chintu, C., Bhat, G., Kapakala, T., Mumba, P. & Nyalungwe, K., 2004. Congenital trypanosomiasis. Journal of Tropical Pediatrics, 50 (6): 377 - 381.
Ngoma: School of Medicine, Department of Paediatrics and Child Health, PO Box 50110, Lusaka, Zambia. [[email protected]]
The last successfully treated case of congenital trypanosomiasis in Zambia was in October 1978, with detailed analysis of immunoglobulins, illustrating the waning of blood and serum levels of IgA, IgG, and IgM during treatment, up to 99 days after treatment. Twenty-five years later, we report on a case of congenital trypanosomiasis. The disease is now rare and can be missed or dismissed as retroviral disease, particularly in adults. The main unusual symptoms were the prolonged intermittent convulsions in an otherwise well infant. Management of the disease is now more interdisciplinary, resources for laboratory support are fewer, lumbar puncture is more relevant, and antitrypanosomal drugs are more difficult to obtain. The mother died within one week of hospitalization and the infant initially responded to three doses of suramin and 3 weeks of melsopropol. Convulsions ceased during the second round of melsopropol. Unfortunately, the infant died of nosocomial infection.
[See also 28: 13088, 13124]
13129 Buguet, A., Bisser, S., Josenando, T., Chapotot, F. & Cespuglio, R., 2005. Sleep structure: a new diagnostic tool for stage determination in sleeping sickness. Acta Tropica, 93 (1): 107 - 117.
Buguet: EA 3734 Neurobiologie des états de Vigilance, IFR-19, Claude-Bernard-Lyon 1 University, 8 Avenue Rockefeller, 69373 Lyon Cedex 08, France.
Human African trypanosomiasis (HAT), due to the transmission of Trypanosoma brucei gambiense and T. b. rhodesiense by tsetse flies, is re-emerging in intertropical Africa. It evolves from the hemolymphatic Stage I to the meningo-encephalitic Stage II. The latter is generally treated with melarsoprol, an arseniate often provoking a deadly encephalopathy. A precise determination of the HAT evolution stage is therefore crucial. Stage II patients show: (i) a deregulation of the 24-h distribution of the sleep-wake alternation; (ii) an alteration of the sleep structure, with frequent sleep onset rapid eye movement (REM) periods (SOREMPs). Gambian HAT was diagnosed in eight patients (four, Stage II; three, Stage I; one, "intermediate" case) at the trypanosomiasis clinic at Viana (Angola). Continuous 48-h polysomnography was recorded on Oxford Medilog 9000-II portable systems before and after treatment with melarsoprol (Stage II) or pentamidine (Stage I and "intermediate" stage). Sleep traces were visually analyzed in 20-s epochs using the PRANA software. Stage II patients showed the complete sleep-wake syndrome, partly reversed by melarsoprol 1 month later. Two Stage I patients did not experience any of these alterations. However, the "intermediate" and one Stage I patients exhibited sleep disruptions and/or SOREMPs, persistent after pentamidine treatment. Polysomnography may represent a diagnostic tool to distinguish the two stages of HAT. Especially, SOREMPs appear shortly after the central nervous system invasion by trypanosomes. The reversibility of the sleep-wake cycle and sleep structure alterations after appropriate treatment constitutes the basis of an evaluation of the healing process.
13130 Girard, M., Giraud, S., Courtioux, B., Jauberteau-Marchan, M.-O. & Bouteille, B., 2004. Endothelial cell activation in the presence of African trypanosomes. [human bone marrow endothelial cell] Molecular and Biochemical Parasitology, 139 (1): 41 - 49.
Girard: EA 3174 Neuroparasitologie et Neuroépidémiologie Tropicales, Faculté de medecine, Limoges, France.
During human African trypanosomiasis, trypanosomes (Trypanosoma brucei gambiense or T. b. rhodesiense) invade the central nervous system (CNS). Mechanisms of blood-brain barrier and blood-cerebrospinal fluid barrier leakage remain unknown. To better understand the relationships between trypanosomes and endothelial cells, the principal cell population of those barriers, we cultured a human bone marrow endothelial cell (HBMEC) line in the presence or absence of T. b. gambiense, to study cell activation. As indicated by NF-êB translocation to the nucleus, cells were activated in the presence of trypanosomes. The expression of the adhesion molecules ICAM-1, E-selectin and VCAM-1 increased in co-culture. The parasites induced the synthesis of the pro-inflammatory cytokines TNF-á, IL-6 and IL-8, and of nitric oxide (NO) by HBMEC. Cells were also cultured in the presence of parasite variant surface glycoproteins (VSGs), and an increase in TNF-á, IL-6, IL-8, and NO synthesis was also observed. Soluble VSGs induced NF-êB translocation, and the expression of adhesion molecules, indicating that they could possibly be the molecular soluble factor responsible for endothelial cell activation. The permeability coefficient of the HBMEC layer increased when cells were cultured in the presence of trypanosomes, parasite culture supernatant, or VSGs. Thus, T. b. gambiense can activate endothelial cells in vitro, through the release of soluble activating factors. Consequences of endothelial cell activation by parasite products may include a potentiation of the inflammatory reaction, leukocyte recruitment, passage of trypanosomes into the CNS, and barrier dysfunction observed during CNS involvement of HAT.
13131 Lejon, V. & Büscher, P., 2005. Cerebrospinal fluid in human African trypanosomiasis: a key to diagnosis, therapeutic decision and post-treatment follow-up. [Review] Tropical Medicine and International Health, 10 (5): 395 - 403.
Lejon: Department of Parasitology, Institute of Tropical Medicine, Nationalestraat 155, 2000 Antwerpen, Belgium. [[email protected]]
Human African trypanosomiasis is a lethal parasitic infection with neurological involvement. Examination of the cerebrospinal fluid (CSF) plays an essential role in diagnosis, selection of treatment and post-treatment follow-up. This paper reviews clinical presentation, diagnosis and treatment of the disease, with emphasis on CSF characteristics and interpretation of the CSF results for therapeutic decision and post-treatment follow-up.
13132 Lugli, E.B., Pouliot, M., Portela, M. del P.M., Loomis, M.R. & Raper, J., 2004. Characterization of primate trypanosome lytic factors. Molecular and Biochemical Parasitology, 138 (1): 9 - 20.
Raper: Department of Medical and Molecular Parasitology, New York University School of Medicine, 341, East 25th Street, New York, NY 10010, USA.
Humans are one of the few species that resist infection by Trypanosoma brucei brucei because the parasites are killed by lytic factors found in human serum. Trypanosome lytic factors (TLFs) are protein/lipid complexes that contain apolipoprotein A-I (apoA-I), and are therefore a class of high density lipoproteins (HDLs). Haptoglobin-related protein (Hpr) is a unique protein component of TLFs, and its expression has only been demonstrated in humans. Trypanolytic activity has only been found in the sera of five primates: humans, gorillas, mandrills, baboons and sooty mangabeys. We describe here previously unidentified components of highly purified human TLF1: apolipoprotein L-I (apoL-I), human cathelicidin antimicrobial peptide 18 (hCAP18) and glycosyl-phosphatidylinositol-specific phospholipase D (GPI-PLD). However, we found that hCAP18 and GPI-PLD, along with apoA-I, are common components of both lytic and non-lytic primate HDLs. In contrast, Hpr, which has been previously implicated as the main lytic component of TLF1, was a unique component of all trypanolytic primate HDLs. Furthermore, a polyclonal antiserum to Hpr neutralised the lytic activity from humans and baboons. ApoL-I, a candidate lytic component of human serum, was not immunologically or genetically detectable in two primate species with lytic activity. Polyclonal antiserum to apoL-I also did not neutralise TLF activity in a total human HDL preparation. These findings suggest that apoL-I is not essential in all primate TLFs, and apoL-I alone is not sufficient for optimal trypanosome lytic activity in human TLF.
13133 Lundkvist, G.B., Kristensson, K. & Bentivoglio, M., 2004. Why trypanosomes cause sleeping sickness. Physiology, 19 (4): 198 - 206.
Kristensson: Department of Neuroscience, Karolinska Insitutet, Stockholm, SE-171 77 Sweden. [[email protected]]
African trypanosomiasis or sleeping sickness is hallmarked by sleep and wakefulness disturbances. In contrast to other infections, there is no hypersomnia, but the sleep pattern is fragmented. This overview discusses how the causative agents, the parasites Trypanosoma brucei, target circumventricular organs in the brain, causing inflammatory responses in hypothalamic structures that may lead to dysfunctions in the circadian-timing and sleep-regulatory systems.
13134 Lutumba, P., Robays, J., Miaka, C., Kande, V., Simarro, P.P., Shaw, A.P.M., Dujardin, B. & Boelaert, M., 2005. Efficience de différentes stratégies de détection de la trypanosomiase humaine Africaine à T. b. gambiense [Efficiency of different detection strategies concerning human African trypanosomiasis due to T. b. gambiense.] Tropical Medicine and International Health, 10 (4): 347 - 356.
Boelaert: Unité d’épidémiologie, Institut de Médecine Tropicale Prince Léopold, Nationalestraat 155, 2000 Anvers, Belgique. [[email protected]]
Population screening for human African trypanosomiasis (HAT) is often based on a combination of two screening tests: lymph node palpation (LN) and card agglutination test for trypanosomiasis (CATT). This decision analysis compared the efficiency of three alternative detection strategies: screening by LN only, CATT only and their combination (LN and CATT). An HAT detection strategy was defined as the sequence of screening and confirmation. Efficacy was evaluated in terms of lives saved. The cost of screening and confirmation tests was estimated in US$. The different parameters in the decision tree were based on published literature and observations of the HAT control programme in the Democratic Republic of Congo. A sensitivity analysis was carried out on those parameters subject to uncertainty. The cost-effectiveness of a detection strategy based on CATT was US$125 per life saved, compared with US$517 for LN and US$452 for the combined. Marginal cost to add LN to CATT only was between US$1 225 and US$5 000 per life saved. Sensitivity analysis shows that these results are robust to variation. The CATT strategy was the most efficient. None of the strategies was able to avoid more than 60 percent of HAT deaths. This moderate efficacy is due to the low sensitivity of the confirmatory (diagnostic) tests. Substantial efficiency gains can be obtained by adopting a CATT only strategy and resources can be better allocated to more sensitive confirmatory tests or to increasing the coverage of populations at risk.
13135 Monteiro, R.Q., Campana, P.T., Melo, P.A. & Bianconi, M.L., 2004. Suramin interaction with human á-thrombin: inhibitory effects and binding studies. International Journal of Biochemistry & Cell Biology, 36 (10): 2077 - 2085.
Monteiro: Departamento de Bioquímica Médica, ICB/CCS, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil. [[email protected]]
Suramin is a hexasulfonated naphthylurea commonly used as antitrypanosomal drug and more recently for the treatment of malignant tumours. Here we show that suramin binds to human á-thrombin inhibiting both the hydrolysis of the synthetic substrate S-2238 (IC50=40 mM), and the thrombin-induced fibrinogen clotting (IC50=20 mM). The latter is completely reversed by albumin (30 mg mL-1) suggesting that, at therapeutic concentrations, suramin is unable to affect á-thrombin activity in the plasma. Kinetic analysis showed that suramin acts as a non-competitive inhibitor decreasing Vmax without changing the Km for S-2238 hydrolysis. Calorimetric studies revealed two distinct binding sites for suramin in á-thrombin. In addition, circular dichroism studies showed that suramin causes significant changes in á-thrombin tertiary structure, without affecting the secondary structure content. Interaction with á-thrombin resulted in an increased fluorescence emission of the drug. Complex formation was strongly affected by high ionic strength suggesting the involvement of electrostatic interactions. Altogether our data suggest that part of the biological activities of suramin might be related to á-thrombin inhibition at extra-vascular sites.
13136 Rock, R.B., Gekker, G., Hu, S.X., Sheng, W.S., Cheeran, M., Lokensgard, J.R. & Peterson, P. K., 2004. Role of microglia in central nervous system infections. Clinical Microbiology Reviews, 17 (4): 942 - 964.
Peterson: Neuroimmunology Laboratory, Minneapolis Medical Research Foundation, and University of Minnesota Medical School, Minneapolis, Minnesota Department of Medicine, Hennepin County Medical Center, 701 Park Ave., Minneapolis, MN 55415 USA. [[email protected].]
The nature of microglia fascinated many prominent researchers in the 19th and early 20th centuries, and in a classic treatise in 1932, Pio del Rio-Hortega formulated a number of concepts regarding the function of these resident macrophages of the brain parenchyma that remain relevant to this day. However, a renaissance of interest in microglia occurred toward the end of the 20th century, fuelled by the recognition of their role in neuropathogenesis of infectious agents, such as human immunodeficiency virus type 1, and by what appears to be their participation in other neurodegenerative and neuroinflammatory disorders. During the same period, insights into the physiological and pathological properties of microglia were gained from in vivo and in vitro studies of neurotropic viruses, bacteria, fungi, parasites, and prions, which are reviewed in this article. New concepts that have emerged from these studies include the importance of cytokines and chemokines produced by activated microglia in neurodegenerative and neuroprotective processes and the elegant but astonishingly complex interactions between microglia, astrocytes, lymphocytes, and neurons that underlie these processes. It is proposed that an enhanced understanding of microglia will yield improved therapies of central nervous system infections, since such therapies are, by and large, sorely needed.
13137 Truc, P., 2003. About Trypanosoma brucei gambiense, the causative agent of the chronic form of Human African Trypanosomiasis: some findings and proposals. African Journal of Biotechnology, 2 (12): 657 - 661
Truc: Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC), Department of Research and Control of Human African Trypanosomiasis, BP 288, Yaounde, Cameroon. [[email protected]]
Since its discovery at the beginning of 20th century, Human African Trypanosomiasis or sleeping sickness has killed several hundred thousands of individuals in Africa, mainly in the central part of the continent. The present status of the disease in several countries is dramatic, such as the Sudan, Democratic Republic of Congo or Angola. However, diagnosis is still based on the detection of parasites in blood or lymphatic juice by microscopy, as in the 1930s. Furthermore, since the discovery of melarsoprol in 1949, no new drugs for treatment have been synthesized. We have to see HAT as coming under the head of ‘most-neglected diseases’ but some findings obtained through biotechnology are discussed in terms of epidemiology and control applications.
[See also 28: 13087, 13088, 13090, 13129]
13138 Deterding, A., Dungey, F.A., Thompson, K.A. & Steverding, D., 2005. Anti-trypanosomal activities of DNA topoisomerase inhibitors. Acta Tropica, 93 (3): 311 - 316.
Steverding: School of Medicine, Health Policy and Practice, University of East Anglia, Norwich NR4 7TJ, UK.
Only four drugs are available for chemotherapy of human African sleeping sickness and these have undesirable toxic side effects. The development of new anti-trypanosomal drugs is, therefore, urgently required. In this study, 15 DNA topoisomerase inhibitors, including approved anti-cancer drugs, were tested for in vitro activity against bloodstream forms of Trypanosoma brucei and human leukaemia HL-60 cells. All compounds exhibited anti-trypanosomal activity, with ED50 values ranging between 3 nM and 30 ìM, and MIC values between 100 nM and >100 ìM. The trypanocidal activities of the most effective DNA topoisomerase inhibitors, aclarubicin, doxorubicin and mitoxantrone, were comparable with those of commercial anti-trypanosomal drugs. These data support the use of DNA topoisomerase inhibitors as lead compounds for anti-trypanosomal drug development.
13139 Miezan T.W., Dje N.N., Doua F. & Boa F., 2002. Trypanosomose humaine africaine en Côte d’Ivoire: caractéristiques biologiques après traitement. A propos de 812 cas traités dans le foyer de Daloa (Côte d’Ivoire). [Human trypanosomiasis in Côte d’Ivoire (Ivory Coast): biological characteristics after treatment. A study of 812 cases treated in the Daloa focus (Côte d’Ivoire).] Bulletin de la Société de Pathologie exotique, 95 (5): 362 - 365.
Miezan: Projet de recherches cliniques sur la trypanosomiase, BP 1425 Daloa, Côte d’Ivoire.
The treatment and post-therapeutic follow up of patients diagnosed with HAT are important for HAT control. A longitudinal survey was implemented in the focus of Daloa (Côte d’Ivoire). A total of 812 patients infected with Trypanosoma brucei gambiense in meningoencephalitic stage and treated with melarsoprol were included; this study focussed on the biological characteristics of patients after treatment. The relapse occurs between 1 and 24 months after treatment. It is essentially neurological, and characterised by the presence in the CSF of antibodies, by the increase of cell count compared with value immediately after treatment, or by the presence of trypanosomes. The cure can be confirmed from 18 months after treatment, and is characterised by the absence of antibodies and trypanosomes in the CSF, by a normal cell count and a normal proteinorachy. However, some biological damage was noted in some patients by the end of the 18-month follow-up period but no relapses occurred amongst them.
13140 Moore, A.C., 2005. Prospects for improving African trypanosomiasis chemotherapy. Journal of Infectious Diseases, 191 (11): 1793 - 1795.
Moore: Division of Parasitic Diseases, M/S F-22, Centers for Disease Control and Prevention, 4770 Buford Hwy., Atlanta, GA 30341 USA. [[email protected]].
Nearly a century ago, specific antimicrobial agents for the treatment of human African trypanosomiasis (HAT) were among the first achievements in the new science of drug discovery and development. However, few advances in HAT chemotherapy have been made in recent decades, and patients today are usually treated with drugs that were introduced before 1950. The infection is transmitted only in rural Africa and does not have a profitable market that would encourage drug development. This lack of progress is part of a larger trend in the global pharmaceutical industry. Investment in treatment for tropical parasitic diseases has plummeted, despite the increasing health burden of these infections. Less than 1 percent of the new chemical entities introduced during the mid-1970s through 1999 were developed for tropical disease indications, and few candidate drugs are in development. Insufficient financial return has not only discouraged research and development but also caused companies to withdraw existing antiparasitic drugs from the market. Five years ago, when virtually every drug capable of curing central nervous system (CNS) infection was no longer produced or was threatened, it appeared that HAT might become untreatable. At present, these drugs are back in production and are available from the World Health Organization (WHO) through donation programs, but a method to ensure availability for the long term has not been identified. The current serious resurgence of the disease and the present inadequacy of the available drugs to treat it are described. Trials of new drugs and improved methods of applying the existing drugs give hope for some improvement in the present serious situation.
13141 Pépin, J. & Mpia, B., 2005. Trypanosomiasis relapse after melarsoprol therapy, Democratic Republic of Congo, 1982-2001. Emerging Infectious Diseases, 11 (6): 921 - 927.
Pépin: Centre for International Health, 3001, 12ème Avenue Nord, Sherbrooke, Québec J1H 5N4, Canada. [[email protected]]
Recently, a high proportion of patients with late-stage Trypanosoma brucei gambiense trypanosomiasis, that had been treated with melarsoprol in some disease-endemic areas, subsequently relapsed. To determine whether the frequency of post-melarsoprol relapses increased over time, we reviewed data from 2 221 trypanosomiasis patients treated with melarsoprol during this period in Nioki, Democratic Republic of Congo, from 1982 to 2001. The frequency of relapses was 5.6 percent (31/553), 6.8 percent (35/512), 4.5 percent (18/398), 11.4 percent (34/299), and 5.0 percent (17/343) for those treated from 1982 to 1985, 1986 to 1989, 1990 to 1993, 1994 to 1997, and 1998 to 2001, respectively. The higher frequency of relapses in 1994 to 1997 was associated with an incremental dosage regimen of melarsoprol. In multivariate analysis, after adjustment for treatment regimen, sex, residence, and trypanosomes in cerebrospinal fluid, post-melarsoprol relapses were shown not to have increased in Nioki, perhaps because 1) little drug pressure exists; 2) sub-therapeutic doses have rarely been administered; 3) little potential exists for the preferential transmission of melarsoprol-resistant strains.
13142 Sanchez-Delgado, R.A. & Anzellotti, A., 2004. Metal complexes as chemotherapeutic agents against tropical diseases: Trypanosomiasis, malaria and leishmaniasis. Mini-Reviews in Medicinal Chemistry, 4 (1): 23 - 30.
Sanchez-Delgado: Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 21827 Caracas 1020-A, Venezuela.
Parasitic diseases represent a major world health problem with very limited therapeutic options, most of the available treatments being decades old and suffering from limited efficacy and/or undesirable collateral effects. The use of metal complexes as chemotherapeutic agents against these ailments appears as a very attractive alternative. Although the design of metal complexes with good therapeutic index is still rather empirical, a number of potential metal-based antiparasitic drugs have become available. In this review, advances in the use of metal complexes for the treatment of trypanosomiasis, malaria, and leishmaniasis as important representatives of the general area of tropical diseases are described.
13143 Schmid, C., Nkunku, S., Merolle, A., Vounatsou, P. & Burri, C., 2004. Efficacy of 10-day melarsoprol schedule 2 years after treatment for late-stage gambiense sleeping sickness. Lancet, 364 (9436): 789 - 790.
Burri: Swiss Tropical Institute, 4002 Basel, Switzerland. [[email protected]]
In 2000, we reported that a new short treatment schedule of melarsoprol was not worse than the longer and demanding standard treatment for late-stage human African trypanosomiasis. This alternative schedule was assessed in an open, randomised clinical equivalence trial of 500 patients in Angola. At 24h after treatment, all patients were parasite free. Of 442 patients, 12 (3 percent) had relapsed after one year, of whom seven (3 percent) had had standard treatment and five (2 percent) the alternative treatment. After two years, 23 (5 percent) relapsing patients were reported, 11 (5 percent) in the standard treatment group and 12 (6 percent) in the new group. The results at the two-year follow-up support and strengthen our previous findings.
13144 Schmid, C., Richer, M., Bilenge, C.M.M., Josenando, T., Chappuis, F., Manthelot, C.R., Nangouma, A., Doua, F., Asumu, P.N., Simarro, P.P. & Burri, C., 2005. Effectiveness of a 10-day melarsoprol schedule for the treatment of late-stage human African trypanosomiasis: Confirmation from a multinational study (IMPAMEL II). Journal of Infectious Diseases, 191 (11): 1922 - 1931.
Burri: Swiss Tropical Institute, Socinstrasse 57, CH-4002 Basel, Switzerland. [[email protected]]
Treatment of late-stage human African trypanosomiasis (HAT) with melarsoprol can be improved by shortening the regimen. A previous trial demonstrated the safety and efficacy of a 10-day treatment schedule. We demonstrate the effectiveness of this schedule in a non-controlled, multinational drug-utilization study. A total of 2 020 patients with late-stage HAT were treated with the 10-day melarsoprol schedule in 16 centres in seven African countries. We assessed outcome on the basis of major adverse events and the cure rate after treatment and during two years of follow-up. The cure rate 24 h after treatment was 93.9 percent; two years later, it was 86.2 percent. However, 49.3 percent of patients were lost to follow-up. The overall fatality rate was 5.9 percent. Of treated patients, 8.7 percent had an encephalopathic syndrome that was fatal 45.5 percent of the time. The rate of severe bullous and maculopapular eruptions was 0.8 percent and 6.8 percent, respectively. The 10-day treatment schedule was well implemented in the field and was effective. It reduces treatment duration, drug amount, and hospitalization costs per patient, and it increases treatment-centre capacity. The shorter protocol has been recommended by the International Scientific Council for Trypanosomiasis Research and Control for the treatment of late-stage HAT caused by Trypanosoma brucei gambiense.
13145 Sternberg, J.M., 2004. Human African trypanosomiasis: clinical presentation and immune response. Parasite Immunology, 26 (11 - 12): 469 - 476.
Sternberg: School of Biological Sciences, University of Aberdeen, Aberdeen AB24 2TZ, UK.
Human African trypanosomiasis or sleeping sickness is caused by infection with two subspecies of the tsetse-fly-vectored haemoflagellate parasite Trypanosoma brucei. Historically, epidemic sleeping sickness has caused massive loss of life, and related animal diseases have had a crucial impact on development in sub-Saharan Africa. After a period of moderately successful control during the mid-part of the 20th century, sleeping sickness incidence is currently rising, and control is hampered by a combination of factors, including civil unrest and the possible development of drug resistance by the parasites. The prevailing view is that the disease is invariably fatal without anti-trypanosomal drug treatment. However, there have also been intriguing reports of wide variations in disease severity as well as evidence of asymptomatic carriers of trypanosomes. These differences in the presentation of the disease will be discussed in the context of our knowledge of the immunology of trypanosomiasis. The impact of dysregulated inflammatory responses in both systemic and CNS pathology will be examined and the potential for host genotype variation in disease severity and control will be discussed.
